PRODUCTION OF FETA CHEESE WITH A REDUCED SALT CONTENT

Sodium chloride (NaCl) is crucial for proper functioning of the organism and plays a key role in many physiological processes. However, excessive sodium intake causes health disorders like elevated blood pressure, heart and cardiovascular diseases. Within the strategy based on lowering the NaCl intake in the Republic of Croatia, thus food production with the lower salt content is encouraged. Cheese is one of the foodstuffs that is widely consumed and has a high ratio of salt especially cheese in brine. This study aimed to investigate whether the replacement of 50% of NaCl with micronized salt in brine influences the physicochemical and sensory properties of feta cheese during maturation. Because of its larger surface area, micronized salt increases the salinity and, thus smaller amounts can be added into the foodstuff compared to the classic NaCl. Analyses of texture, salt content, physicochemical and sensory analyses were performed after 7, 14, 21 and 28 days of cold storage. Based on the results it can be concluded that micronized NaCl may serve as a replacement for NaCl up to 50% without significant change in the physicochemical and sensory properties of the cheese compared to the control sample

Ispitivanje kvaliteta i antimikrobne aktivnosti gajenog nevena, Calendula officinalis L.

Introduction: Marigold flower, Calendula officinalis L, Asteraceae, is traditionally used to treat skin diseases. Marigold flowers contain triterpenoid saponins, carotenoids, flavonoids and essential oil. Extracts and essential oil exhibit anti-inflammatory, antioxidant and antimicrobial activity. Aim: The aim of the study was to investigate quality of cultivated Calendulae flos, to compare flavonoids content in inflorescence and ligulate florets and to determine antimicrobial activity of extract and traditional ointment based on marigold. Material and Methods: Plant material was collected from private gardens in Kikinda, Mokrin and Vrnjacka Banja during September and November 2015. Quality investigation included: macroscopic and microscopic analysis and determination of the specific quality according to the monograph of European Pharmacopoeia 7.0. The identification of flavonoids was carried out by HPLC. Antimicrobial activity of ethanol extracts (1:20) and traditional ointment based on ligulate florets or whole inflorescences was tested against six standard laboratory strains by agar-diffusion method. Results: Macroscopic and microscopic characteristics and content of flavonoids (2.0-2.76%) in the ligulate florets of cultivated marigold corresponded to the requirements of Ph. Eur. 7.0. Separated ligulate florets (2.76 ± 0.01%) contained a higher concentration of flavonoids than whole inflorescence (1.68 ± 0.0%). Also, in ligulate florets differences were found in the flavonoids content during September (2.76 ± 0.01%) and November (1.45 ± 0.01%), while in whole inflorescences concentration didn't significantly change. In all tested samples 3-O-heterosides of quercetin and isorhamnetin were identified. The ethanol extracts of ligulate florets, whole inflorescence as well as traditional ointments showed the antimicrobial activity. The traditional ointment based on ligulate florets showed stronger antimicrobial effect than the ointment based on full inflorescences. Conclusion: Quality investigation showed that cultivated marigold flowers meet the requirements of Ph. Eur. 7.0. Ligulate florets contained more flavonoids than whole inflorescences. Extracts and traditional ointment based on ligulate florets showed antimicrobial activity, which confirmed long-term use of marigold.Uvod: Cvast nevena, Calendula officinalis L., Asteraceae, tradicionalno se koristi za lečenje kožnih bolesti. Cvast nevena sadrži triterpenske saponine, karotenoide, flavonoide i etarsko ulje. Ekstrakti i etarsko ulje cvasti nevena pokazuju antiinflamatornu, antioksidantnu i antimikrobnu aktivnost. Cilj rada: Cilj rada je bio ispitivanje kvaliteta cvasti gajenog nevena, Calendulae flos, upoređivanje sadržaja flavonoida u cvasti i jezičastim cvetovima, kao i utvrđivanje antimikrobne aktivnosti ekstrakata i tradicionalne masti na bazi nevena. Materijal i metode: Biljni materijal je prikupljen iz privatnih bašti u Kikindi, Mokrinu i Vrnjačkoj Banji tokom septembra i novembra 2015. godine. Ispitivanje kvaliteta je obuhvatalo makroskopsku i mikroskopsku analizu i određivanje specifičnog kvaliteta prema monografiji Evropske farmakopeje 7.0. Identifikacija flavonoida je izvršena metodom tečne hromatografije pod visokim pritiskom (HPLC). Antimikrobna aktivnost etanolnih ekstrakata (1:20) i tradicionalnih masti na bazi jezičastih cvetova ili celih cvasti ispitivana je na šest standardnih laboratorijskih sojeva agar-difuzionim matodom. Rezultati: Makroskopske i mikroskopske karakteristike i sadržaj flavonoida (2,0-2,76%) u jezičastim cvetovima gajenog nevena odgovarali su zahtevima propisanom u Ph.Eur. 7.0. Izdvojeni jezičasti cvetovi (2,76 ± 0,01%) sadržali su veću koncentraciju flavonoida od celih cvasti (1,68 ± 0,0%). U jezičastim cvetovima su uočene i razlike u sadržaju flavonoida tokom septembra (2,76 ± 0,01%) i novembra (1,45 ± 0,01%), dok se u celim cvetovima koncentracija nije značajno menjala. U svim ispitivanim uzorcima identifikovani su 3-O-heterozidi kvarcetina i izoramnetina. Antimikrobno delovanje su pokazali etanolni ekstrakti jezičastih i celih cvetova, kao i tradicionalne masti. Tradicionalna mast na bazi jezičastih cvetova pokazala je izraženiji antimikrobni efekat od masti na bazi celih cvasti. Zaključak: Ispitivanje kvaliteta je pokazalo da cvast gajenog nevena odgovara zahtevima Ph.Eur.7.0. Jezičasti cvetovi su sadržali više flavonoida od celih cvasti nevena. Ekstrakti i tradicionalna mast na bazi jezičastih cvetova pokazali su antimikrobnu aktivnost, što potvrđuje dugogodišnju upotrebu nevena

Potential genomic biomarkers of obesity and its comorbidities for phthalates and bisphenol A mixture: In silico toxicogenomic approach

This in silico toxicogenomic study aims to explore the relationship between phthalates and bisphenol A (BPA) co-exposure and obesity, as well as its comorbid conditions, in order to construct a possible set of genomic biomarkers. The Comparative Toxicogenomics Database (CTD; http://ctd.mdibl.org) was used as the main data mining tool, along with GeneMania (https://genemania.org), ToppGene Suite (https://toppgene.cchmc.org) and DisGeNET (http://www. disgenet.org). Among the phthalates, bis(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) were chosen as the most frequently curated phthalates in CTD, which also share similar mechanisms of toxicity. DEHP, DBP and BPA interacted with 84, 90 and 194 obesity-related genes/proteins, involved in 67, 65 and 116 pathways, respectively. Among these, 53 genes/proteins and 42 pathways were common to all three substances. 31 genes/proteins had matching interactions for all three investigated substances, while more than half of these genes/proteins (56.49%) were in co-expression. 7 of the common genes/proteins (6 relevant to humans: CCL2, IL6, LPL, PPARG, SERPINE1, and TNF) were identified in all the investigated obesity comorbidities, while PPARG and LPL were most closely linked to obesity. These genes/proteins could serve as a target for further in vitro and in vivo studies of molecular mechanisms of DEHP, DBP and BPA mixture obesogenic properties. Analysis reported here should be applicable to any mixture of environmental chemicals and any disease present in CTD

LONG-TERM GLUCOCORTICOID THERAPY AND THE RAPID DEVELOPMENT OF SQUAMOUS CELL CARCINOMA IN SYSTEMIC SCLEROSIS: IS THERE A CONNECTION?

Sistemska skleroza (SSc) autoimunosna je bolest, koju prati rizik od razvoja malignoma, posebice karcinoma pluća, među kojima se prema učestalosti ističu adenokarcinom i planocelularni karcinom. Šezdesettrogodišnja bolesnica sa SSc-om hospitalizirana je zbog nesvjestice, lošeg općeg stanja i gangrenoznih promjena okrajina. Zbog epileptičkih napadaja koji su uslijedili te popratne ljevostrane slabosti učinjena je kompjutorizirana tomografi ja (CT) neurokranija koja je otkrila lezije tipa rasadnica (metastaza). Na CT-u pluća bila je vidljiva novotvorina u desnom hilusu koja je patohistološki evaluirala kao planocelularni karcinom 2. stupnja. Bolesnica je nakon jednomjesečne hospitalizacije uz potpornu terapiju, u klinički poboljšanom stanju, otpuštena na kućnu njegu s preporukom daljnjeg onkološkog liječenja, no nekoliko dana potom je preminula. S obzirom na adenokarcinome, planocelularni karcinomi pluća uobičajeno se razvijaju u znatno dužem razdoblju te držimo da je atipično ubrzan njegov razvoj u ove bolesnice potaknut imunosupresivnim djelovanjem srednje visokih doza glukokortikoida koje je bolesnica samoinicijativno uzimala više godina.Systemic sclerosis (SSC) is an autoimmune disease associated with the risk of malignancies, especially lung cancer, among which adenocarcinoma and squamous cell carcinoma are the most frequent. A 63-year-old female patient with SSC was hospitalized due to blackouts, poor general condition, and changes in her fi ngers. Because of subsequent epileptic seizures resulting in weakness of the left side of her body, computerized tomography (CT) of the neurocranium was performed which showed metastatic lesions. A CT scan of the thoracic organs displayed pulmonary neoplasia in the right hilum, which were histologically evaluated as grade 2 squamous cell carcinoma. Aft er one month of hospitalization with supportive therapy, the patient’s clinical condition improved, and she was discharged into home care with recommendations for further oncological treatment. However, the patient died several days later. In comparison to adenocarcinomas, squamous cell carcinomas of the lungs usually develop through a signifi cantly longer period. We consider that the unusually rapid development of the carcinoma in this patient was stimulated by the immunosuppressive eff ect of high doses of glucocorticoids that she had been taking for several years on her own initiative

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POLYMYALGIA RHEUMATICA, GIANT CELL ARTERITIS AND MALIGNANCY – IS THERE AN ASSOCIATION?

Reumatska polimialgija (PMR) i temporalni arteritis (TA) česte su upalne reumatske bolesti u osoba starijih od pedeset godina. Usko su povezane i često se pojavljuju u istog bolesnika. Uobičajeni simptomi su bol i nelagoda te zakočenost mišića ramenog obruča, vrata i kukova, a praćeni su povišenim vrijednostima upalnih reaktanata i anemijom kronične bolesti. Uz navedeno u TA se javlja temporalna glavobolja, smetnje vida i sluha te bol čeljusti. Dobar i brz terapijski odgovor na primjenu glukokortikoida ključno je obilježje ovih dvaju poremećaja. Kod nekih upalnih autoimunih reumatskih bolesti zabilježena je veća incidencija malignoma. Premda razlozi te veće pojavnosti nisu jasni, smatra se da je u podlozi poremećena regulacija imunosnog sustava. Više prikaza slučaja, serija slučaja i epidemioloških studija sugerira poveći rizik od malignih bolesti u bolesnika s PMR i TA, ali su rezultati epidemioloških studija kontradiktorni. U svrhu istraživanja ove povezanosti nedavno je provedena nekolicina prospektivnih istraživanja. Povišen rizik malignih oboljenja u bolesnika s PMR/TA nedvojbeno je utvrđen u prvih 6 – 12 mjeseci od dijagnoze, a poslije se taj rizik gubi i izjednačava s rizikom opće populacije. Uočena je veća pojavnost karcinoma urogenitalnog, limfatičkog, hematopoetskog i živčanog sustava. Kako se do dijagnoze PMR i TA dolazi „per exclusionem“, a klinička slika često nije specifična i može nalikovati paraneoplastičkom sindromu, potrebna je vrlo pažljiva klinička evaluacija i pridržavanje klasifikacijskih kriterija. Nužno je razmotriti sve što diferencijalno dijagnostički dolazi u obzir, uključujući malignitet, posebno tijekom prve godine kliničkog praćenja. Unatoč tome u oko 20 % bolesnika s PMR/TA dolazi do naknadne revizije dijagnoze u neku od upalnih reumatskih ili malignih bolesti.Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are two common chronic inflammatory rheumatologic disorders in adults aged over 50 years. These disorders are closely related and commonly occur together. Classic symptoms are bilateral pain, aching, and stiffness in the shoulders and pelvic girdle, usually accompanied by elevated inflammatory markers and anemia of chronic disease. The hallmark of these two diseases is a good and quick response to glucocorticoid therapy. An increased incidence of malignancy has been observed in some autoimmune inflammatory disorders. The mechanism of this association is poorly understood, but is believed to be related to a dysregulation of the immune system. Several case reports and case series have suggested that an increased risk of malignancy also exists in patients with GCA and PMR, but no clear association has been proven due to conflicting data coming from epidemiological studies. Recently, a few larger prospective cohort studies were performed to explore this association. An increased risk of a cancer diagnosis was found within the first 6-12 months after a PMR/GCA diagnosis. The data suggested an excess of cancers of the genitourinary, lymphatic, hematologic, and nervous systems. Beyond that period, the risk of malignancy in PMR/GCA was only slightly elevated, or even equal to the control population. As a diagnosis of PMR and GCA is usually achieved “per exclusionem“, and the clinical presentation is non-specific and may resemble paraneoplastic syndrome, making an accurate diagnosis of these disorders in the elderly population is essential. Clinicians need to be aware of the possibility of alternative diagnoses, including cancer. Thus, patients diagnosed with PMR and GCA should be carefully monitored, especially in the first year after the initial diagnosis, to exclude underlying cancer. In up to 20% of cases of PMR/GCA the diagnosis is subsequently revised to other inflammatory rheumatic disease or malignant disease

Trends in Anti-Tumor Effects of Pseudomonas aeruginosa Mannose-Sensitive-Hemagglutinin (PA-MSHA): An Overview of Positive and Negative Effects

Cancer is a leading cause of death worldwide, for which finding the optimal therapy remains an ongoing challenge. Drug resistance, toxic side effects, and a lack of specificity pose significant difficulties in traditional cancer treatments, leading to suboptimal clinical outcomes and high mortality rates among cancer patients. The need for alternative therapies is crucial, especially for those resistant to conventional methods like chemotherapy and radiotherapy or for patients where surgery is not possible. Over the past decade, a novel approach known as bacteria-mediated cancer therapy has emerged, offering potential solutions to the limitations of conventional treatments. An increasing number of in vitro and in vivo studies suggest that the subtype of highly virulent Pseudomonas aeruginosa bacterium called Pseudomonas aeruginosa mannose-sensitive-hemagglutinin (PA-MSHA) can successfully inhibit the progression of various cancer types, such as breast, lung, and bladder cancer, as well as hepatocellular carcinoma. PA-MSHA inhibits the growth and proliferation of tumor cells and induces their apoptosis. Proposed mechanisms of action include cell-cycle arrest and activation of pro-apoptotic pathways regulated by caspase-9 and caspase-3. Moreover, clinical studies have shown that PA-MSHA improved the effectiveness of chemotherapy and promoted the activation of the immune response in cancer patients without causing severe side effects. Reported adverse reactions were fever, skin irritation, and pain, attributed to the overactivation of the immune response. This review aims to summarize the current knowledge obtained from in vitro, in vivo, and clinical studies available at PubMed, Google Scholar, and ClinicalTrials.gov regarding the use of PA-MSHA in cancer treatment in order to further elucidate its pharmacological and toxicological properties

Conducting bioinformatics analysis to predict sulforaphane-triggered adverse outcome pathways in healthy human cells

Sulforaphane (SFN) is a naturally occurring molecule present in plants from Brassica family. It becomes bioactive after hydrolytic reaction mediated by myrosinase or human gastrointestinal microbiota. Sulforaphane gained scientific popularity due to its antioxidant and anti-cancer properties. However, its toxicity profile and potential to cause adverse effects remain largely unidentified. Thus, this study aimed to generate SFN-triggered adverse outcome pathway (AOP) by looking at the relationship between SFN-chemical structure and its toxicity, as well as SFN-gene interactions. Quantitative structure-activity relationship (QSAR) analysis identified 2 toxophores (Derek Nexus software) that have the potential to cause chromosomal damage and skin sensitization in mammals or mutagenicity in bacteria. Data extracted from Comparative Toxicogenomics Database (CTD) linked SFN with previously proposed outcomes via gene interactions. The total of 11 and 146 genes connected SFN with chromosomal damage and skin diseases, respectively. However, network analysis (NetworkAnalyst tool) revealed that these genes function in wider networks containing 490 and 1986 nodes, respectively. The over-representation analysis (ExpressAnalyst tool) pointed out crucial biological pathways regulated by SFN-interfering genes. These pathways are uploaded to AOP-helpFinder tool which found the 2321 connections between 19 enriched pathways and SFN which were further considered as key events. Two major, interconnected AOPs were generated: first starting from disruption of biological pathways involved in cell cycle and cell proliferation leading to increased apoptosis, and the second one connecting activated immune system signaling pathways to inflammation and apoptosis. In both cases, chromosomal damage and/or skin diseases such as dermatitis or psoriasis appear as adverse outcomes

Synthesis, characterization and antioxidative activity of 1,3-dihydro-3-[4-substituted-(phenylmethyl)imino]-2H-indole-2-ones

Izvršena je sinteza četiri 1,3-dihidro-3-[4-supstituisanih-(fenilmetil)imino]-2H-indol-2-ona i to: 1,3-dihidro-3-[(fenilmetil)imino]-2H-indol-2-ona, 1,3-dihidro-3-[4-brom-(fenilmetil)imino]-2H-indol-2-ona, 1,3-dihidro-3-[4-hidroksi-(fenilmetil) imino]-2H-indol-2-ona, 1,3-dihidro-3-[4-metoksi-(fenilmetil)imino]-2H-indol-2-ona, kao i jedinjenja slične strukture, 1,3-dihidro-3-[(2-feniletil)imino]-2H-indol-2-ona. Urađena je karakterizacija sintetisanih jedinjenja primenom FTIR spektroskopije, određivanjem temperature topljenja i elementalnom analizom, nakon čega je izvršeno ispitivanje antioksidativne aktivnosti svih pet jedinjenja. Antioksidativna aktivnost je određena primenom DPPH (1,1-difenil-2-pikril-hidrazil radikal) metode, u cilju određivanja najefikasinijeg jedinjenja od značaja za dalje istraživanje.The synthesis of 1,3-dihydro-3-[4-substituted-(phenylmethyl)imino]-2H-indole-2-ones: 1,3-dihydro-3-[(phenylmethyl)imino]-2H-indol-2-one, 1,3-dihydro-3-[4-bromo-(phenylmethyl)imino]-2H-indol-2-one, 1,3-dihydro-3-[4-hydroxy-phenyl-methyl)imino]-2H-indol-2-one, 1,3-dihydro-3-[4-methoxy-(phenylmethyl)imino]-2H-indol-2-one, as well as of the compound of similar structure, 1,3-dihydro-3-[(2-phenylethyl)imino]-2H-indol-2-one, was performed. The characterization of the obtained five compounds was carried out using FTIR, melting points and elemental analysis. Their antioxydative activity was then tested by DPPH (2,2-diphenyl-1-picrylhydrazyl radical) method and the results were compared in order to determine the most efficient compound, significant for further research